Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Dina Sameh Soliman ◽  
Ahmad Al-Sabbagh ◽  
Feryal Ibrahim ◽  
Ruba Y. Taha ◽  
Zafar Nawaz ◽  
...  

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.


2009 ◽  
Vol 133 (7) ◽  
pp. 1121-1134 ◽  
Author(s):  
Sandeep Gurbaxani ◽  
John Anastasi ◽  
Elizabeth Hyjek

Abstract Context.—Diffuse large B-cell lymphoma is a heterogenous group of lymphomas. In this review, we present a brief description of the large number of entities recognized in the recently published (2008) World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Objective.—We highlight the unique clinicopathologic and molecular genetic features of these new and previously recognized entities, to illustrate the rational for the development of this classification. To help simplify the understanding of this now large and complex group of diseases, we have attempted to create broader subgroups of related entities. We discuss large B-cell lymphoma that are not otherwise specified, those that are based on anatomic site, those that have unique histology or phenotype or genotype, those that are associated with Epstein-Barr virus or Kaposi sarcoma–associated herpesvirus and herpesvirus 8, and those that are unclassifiable. Data Sources.—World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2008), published literature from PubMed (National Library of Medicine), and primary material from the authors' institution were reviewed. Conclusions.—Recognition of the different subtypes of diffuse large B-cell lymphoma as described in the World Health Organization classification scheme will lead to improved understanding of the unique clinicopathologic and genetic features associated with these subtypes of lymphoma.


Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 284-294 ◽  
Author(s):  
Andrew Davies

AbstractAlthough there have been significant insights into the biology of diffuse large B-cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has been disappointing over the same timeframe. This is not for want of trying. In 2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the “gold standard,” despite all of our insights into cell-of-origin and other subgroups. We have traditionally used clinical risk factors to tailor our therapies and have tested intensification of chemotherapy with little success. We are now in an era of testing therapies according to the molecular phenotype of the individual’s tumor. Many phase 1/2 studies have looked at adding targeted agents to conventional R-CHOP with some promise. The phase 3 data are now starting to emerge. Are we ready yet to modify our standard of care and have we reached an era of precision medicine in DLBCL? The answer to this is “not yet.” The exception is perhaps patients with the newly defined World Health Organization category of high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, the so-called double- and triple-hit lymphomas. In these tumors there has been a move away from R-CHOP to more intensified regimens, however, has not been based upon rigorous prospective evaluation but review of retrospective datasets. This article will review the molecular subgroups of DLBCL, interventional strategies, and the outcomes of these interventions to date.


2006 ◽  
Vol 130 (10) ◽  
pp. 1497-1502 ◽  
Author(s):  
Francisco Vega ◽  
Anthony Padula ◽  
Jose R. Valbuena ◽  
Mirela Stancu ◽  
Dan Jones ◽  
...  

Abstract Context.—Pleural involvement by lymphoma is relatively common. However, there are very few clinicopathologic studies reported in the literature of lymphomas involving the pleura. Objective.—To characterize the clinicopathologic features of lymphomas involving the pleura. Design.—We reviewed the clinicopathologic features of 34 patients with lymphoma involving the pleura proven by biopsy and classified these neoplasms using the World Health Organization classification. Results.—There were 22 men and 12 women, with an average age of 62 years (range, 22–82 years). Nine (26.5%) patients had pleural involvement as the only site of disease, 22 (64.7%) had other sites of involvement, and 3 (8.8%) had inadequate staging data. Eighteen (56.2%) of 32 patients with adequate clinical data had a history of lymphoma (including 3 patients with pleural involvement as the only disease site). In 29 (85.3%) cases, a specific diagnosis according to the World Health Organization classification could be made: 17 (58.6%) diffuse large B-cell lymphoma, 5 (17.2%) follicular lymphoma (including a case with areas of diffuse large B-cell lymphoma), 2 (6.9%) small lymphocytic lymphomas/chronic lymphocytic leukemia, 2 (6.9%) precursor T-cell lymphoblastic lymphoma/leukemia, 1 (3.4%) mantle cell lymphoma, 1 (3.4%) posttransplant lymphoproliferative disorder, and 1 (3.4%) classical Hodgkin lymphoma. The other 5 cases were B-cell lymphomas that could not be further classified. Cytologic examination of pleural fluid was performed in 15 cases and was positive for lymphoma in 8 (53.3%) cases. Conclusions.—Most patients with lymphoma involving the pleura have simultaneous evidence of systemic involvement. The most frequent type is diffuse large B-cell lymphoma, followed by follicular lymphoma. Cytologic examination can have negative results in patients with pleural involvement by lymphoma.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2717
Author(s):  
Paola Chabay

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma (NHL) in adults. Epstein–Barr virus (EBV) positive DLBCL of the elderly was defined by the World Health Organization (WHO) in 2008, it was restricted only to patients older than 50 years old, and it was attributed to immunesenescence associated with physiological aging. After the description of EBV-associated DLBCL in children and young adults, the WHO redefined the definition, leading to the substitution of the modifier “elderly” with “not otherwise specified” (EBV + DLBCL, NOS) in the updated classification, and it is no more considered provisional. The incidence of EBV + DLBCL, NOS varies around the world, in particular influenced by the percentage of EBV+ cells used as cut-off to define a case as EBV-associated. EBV has effect on the genetic composition of tumor cells, on survival, and at the recruitment of immune cells at the microenvironment. In this review, the role of EBV in the pathogenesis of DLBCL is discussed.


Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 590-596 ◽  
Author(s):  
Jonathan W. Friedberg

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.


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